The strongest evidence that cannabis use may be a risk factor for later psychosis comes from a Swedish cohort study which found that heavy cannabis use at age 18 increased the risk of later schizophrenia sixfold. 12 This study could not establish whether adolescent cannabis use was a consequence of pre-existing psychotic symptoms rather than a cause. We present the first prospective longitudinal study of adolescent cannabis use as a risk factor for adult schizophreniform disorder, taking into account childhood psychotic symptoms3 antedating cannabis use.

Association between cannabis use in adolescence and schizophrenia and depressive symptoms and disorders at age 26 (n=759), controlling for childhood psychotic symptoms and use of other drugs in adolescence

Methods and results

The Dunedin multidisciplinary health and development study (a study of a general population birth cohort of 1037 individuals born in Dunedin, New Zealand, in 1972-3)4 has a 96% follow up rate at age 26. It obtained information on psychotic symptoms at age 11 and drug use at ages 15 and 18 from self reports and assessed psychiatric symptoms at age 26 with a standardised interview schedule to obtain DSM-IV (diagnostic and statistical manual of mental disorders, 4th edition) diagnoses. We analysed data from a representative group of 759 (74%) living study members who had complete data on adult psychiatric outcomes, adolescent use of illicit substances, and childhood psychotic symptoms.

We divided the sample into three groups based on cannabis use at ages 15 and 18. The 494 controls (65.1% of the sample) had reported using cannabis “never” or “once or twice” at both ages; cannabis users by age 18 (236; 31.1%) first reported using cannabis “three times or more” at age 18; and cannabis users by age 15 (29; 3.8%) had reported using cannabis “three times or more” at age 15 (all of whom continued to use cannabis at age 18).

Psychiatric outcomes at age 26 were symptoms of schizophrenia and depression and diagnoses of schizophreniform disorder and depression.

Multiple linear regression analyses showed that cannabis users by age 15 and by age 18 had more schizophrenia symptoms than controls at age 26 (table). These results remained significant after psychotic symptoms at age 11 were controlled for. The effect was stronger with earlier use.

Logistic regression analyses showed that people who used cannabis by age 15 were four times as likely to have a diagnosis of schizophreniform disorder at age 26 than controls. After psychotic symptoms at age 11 were controlled for, the risk for adult schizophreniform disorder remained higher among those who used cannabis at age 15; however, this risk was reduced by 31% and was no longer significant.

Cannabis use by age 15 did not predict depressive outcomes at age 26. Use of other drugs in adolescence did not predict schizophrenia outcomes over and above the effect of cannabis use.

Comment

Using cannabis in adolescence increases the likelihood of experiencing symptoms of schizophrenia in adulthood. Our findings agree with those of the Swedish study1 and add three new pieces of evidence. Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding.5 Thirdly, risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression. Our findings now require replication in large population studies with detailed measures of cannabis use and schizophrenia.

Although most young people use cannabis in adolescence without harm, a vulnerable minority experience harmful outcomes. A tenth of the cannabis users by age 15 in our sample (3/29) developed schizophreniform disorder by age 26 compared with 3% of the remaining cohort (22/730). Our findings suggest that cannabis use among psychologically vulnerable adolescents should be strongly discouraged by parents, teachers, and health practitioners. Policy makers and law makers should concentrate on delaying onset of cannabis use.

Contributors: LA participated in the study design, analysed and interpreted the data, and wrote the first draft of the paper. MC and RP participated in the study design and assisted with the analysis and interpretation of the data and the writing of the paper. RM, AC, and TEM participated in the study design and assisted with the interpretation of the data and writing of the paper. RP, AC, and TEM coordinated the collection of the data. LA, RP, and TEM are guarantors of the study.

Footnotes

Editorial by Rey and Tennant

Funding The Dunedin Multidisciplinary Health and Development Research Unit and RP are supported by the New Zealand Health Research Council. This research received support from the Schizophrenia Research Fund, London (MC, AC, TEM), the UK Medical Research Council, the EJLB Foundation (MC) and from US-NIMH grants MH45070 (TEM) and MH49414 (AC). LA is supported by the Canadian Institute of Health Research. TEM is a Royal Society-Wolfson Merit Award holder.